11-66756337-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000525449.6(C11orf80):c.-149-6del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,081,708 control chromosomes in the GnomAD database, including 84 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 31)
  • Exomes 𝑓: 0.016 (72 hom.)
• Consequence: C11orf80 ENST00000525449.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.538

Genes affected

C11orf80 (HGNC:26197): (TOP6B like initiator of meiotic double strand breaks) Predicted to be involved in meiotic DNA double-strand break formation and reciprocal meiotic recombination. Predicted to be located in chromosome. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-66756337-CT-C is Benign according to our data. Variant chr11-66756337-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1659/149214) while in subpopulation NFE AF= 0.0159 (1066/67076). AF 95% confidence interval is 0.0151. There are 12 homozygotes in gnomad4. There are 760 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C11orf80	NM_001302084.2	c.-29-2696del		intron_variant		ENST00000540737.7
C11orf80	NM_024650.3	c.317-6del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C11orf80	ENST00000540737.7	c.-29-2696del		intron_variant		2	NM_001302084.2	A2

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1659 AN: 149118 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00546

Gnomad AMI AF: 0.0298

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0134

Gnomad EAS AF: 0.000391

Gnomad SAS AF: 0.00470

Gnomad FIN AF: 0.00130

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.0411 AC: 1044 AN: 25382 Hom.: 6 AF XY: 0.0407 AC XY: 566 AN XY: 13902

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.0426

Gnomad ASJ exome AF: 0.0536

Gnomad EAS exome AF: 0.0153

Gnomad SAS exome AF: 0.0332

Gnomad FIN exome AF: 0.0309

Gnomad NFE exome AF: 0.0483

Gnomad OTH exome AF: 0.0430

GnomAD4 exome AF: 0.0158 AC: 14737 AN: 932494 Hom.: 72 Cov.: 24 AF XY: 0.0158 AC XY: 7123 AN XY: 450934

Gnomad4 AFR exome AF: 0.00721

Gnomad4 AMR exome AF: 0.0198

Gnomad4 ASJ exome AF: 0.0197

Gnomad4 EAS exome AF: 0.00538

Gnomad4 SAS exome AF: 0.00995

Gnomad4 FIN exome AF: 0.00878

Gnomad4 NFE exome AF: 0.0164

Gnomad4 OTH exome AF: 0.0163

GnomAD4 genome AF: 0.0111 AC: 1659 AN: 149214 Hom.: 12 Cov.: 31 AF XY: 0.0104 AC XY: 760 AN XY: 72734

Gnomad4 AFR AF: 0.00544

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.0134

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.00470

Gnomad4 FIN AF: 0.00130

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0147

Bravo AF: 0.0125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TOP6BL-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs538618909; hg19: chr11-66523808;